Hengrui’s once-weekly dual GLP-1/GIP agonist HRS9531 delivered 48-week mean weight loss of 11.2%, 17.4%, and 19.2% at 2 mg, 4 mg, and 6 mg, respectively, on the hypothetical estimand versus 1.4% on placebo; on the treatment policy estimand, reductions were 10.7%, 16.4%, and 17.7%. At the 6 mg dose, 85.7% achieved at least a 5% loss, and 44.4% reached at least a 20% loss. Discontinuations due to adverse events were low across doses (≤1.4%), with gastrointestinal events predominating, and the safety profile was consistent with that of incretin-based therapies. Cardiometabolic markers, including blood pressure, lipids, insulin resistance measures, and hsCRP, improved.
The core development is twofold: Hengrui presented these Phase 3 data (GEMINI-1; n=567, 48 weeks, China) at ObesityWeek and has an accepted marketing application with China’s NMPA for chronic weight management. In parallel, ex-China partner Kailera plans to initiate a global Phase 3 program by year-end 2025, expanding to higher maintenance doses (8 mg and 10 mg) and longer durations (at least 52 weeks). The global package spans three studies across obesity without diabetes, obesity with type 2 diabetes, and a higher-BMI non-diabetes cohort. Phase 2 results previously reported at 8 mg showed a mean weight loss of 23.6% at week 36, without an apparent plateau, informing the higher-dose strategy moving forward.
Strategically, this is a fast-follow effort positioned against the leading incretin class, where dual agonists have set a high efficacy bar. The China-first path aims to secure near-term approval and a real-world foothold. At the same time, the global sponsor pushes into dose intensification and durability —the two levers most likely to differentiate in a market where weekly injections and class-typical GI tolerability are already normalized. The small delta between hypothetical and treatment-policy estimands suggests robustness to intercurrent events and program discipline at 6 mg; however, the pivot to 8–10 mg is the critical bet, trading potential incremental efficacy for heightened tolerability and adherence risk that can erode net benefit at scale. The emphasis on cardiometabolic risk factor optimization indicates a bid to frame value beyond the scale, anticipating payer and regulatory scrutiny of outcomes that matter for long-term morbidity.
For sites and CROs, the global program implies long-duration, high-throughput recruitment in a crowded obesity trial environment where background use of commercial GLP-1s, concomitant medication policies, and standardized lifestyle counseling complicate execution. Expect tight titration protocols, adherence surveillance, and aggressive retention tactics, with remote weight capture and ePROs for GI events becoming operational mainstays. Regulators will assess how Chinese Phase 3 data translate across diverse global populations and phenotypes, and how higher-dose maintenance regimens perform on tolerability and discontinuation. Vendors supplying peptide manufacturing, autoinjectors, and connected devices will be central to risk management, given class-wide supply volatility and the need to instrument outcomes beyond weight.
Near term, watch the global Phase 3 protocol choices: active comparator versus placebo, titration schedules at 8–10 mg, and whether endpoints extend to durability off-treatment, sleep apnea, or liver health surrogates. The durability signal beyond 48–52 weeks, along with discontinuation trajectories at higher doses, will determine whether KAI-9531 clears the efficacy-tolerability bar set by incumbents. Parallel regulatory engagement in the U.S. and EU, alignment on estimands, and clarity on safety monitoring in diabetes populations will shape timelines. Ultimately, manufacturing readiness and device strategy will be as determinative as the clinical signal in converting promising weight loss into global market presence.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
